The Chromosome Axis Mediates Feedback Control of CHK-2 to Ensure Crossover Formation in C. elegans.

CHK-2 kinase is a master regulator of meiosis in C. elegans. Its activity is required for homolog pairing and synapsis and for double-strand break formation, but how it drives and coordinates these pathways to ensure crossover formation remains unknown. Here we show that CHK-2 promotes pairing and synapsis by phosphorylating a family of zinc finger proteins that bind to specialized regions on each chromosome known as pairing centers, priming their recruitment of the Polo-like kinase PLK-2. This knowledge enabled the development of a phospho-specific antibody as a tool to monitor CHK-2 activity. When either synapsis or crossover formation is impaired, CHK-2 activity is prolonged, and meiotic progression is delayed. We show that this common feedback circuit is mediated by interactions among a network of HORMA domain proteins within the chromosome axis and generates a graded signal. These findings reveal conserved regulatory mechanisms that ensure faithful meiotic chromosome segregation in diverse species.

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